New therapies for uncontrolled severe chronic rhinosinusitis with nasal polyps

Abstract Over the last two decades, there has been a growing comprehension of the pathophysiological processes underlying chronic rhinosinusitis (CRS). This progress has resulted in a shift from phenotyping to endotyping, refocusing attention from eosinophilic inflammation to a more comprehensive consideration of type 2 immunity. Furthermore, conventional perspectives on ventilation and drainage have been replaced by the mucosal concept, influencing therapeutic approaches. The use of endotypes, which are identified based on pathophysiological characteristics, enhances our understanding of the diverse manifestations of CRS. This, in turn, improves the accuracy of diagnosis and informs more effective treatment strategies. Recently, in relation to the underlying immunopathological profile, three types of CRS have been identified, namely: Ty1, Ty2, and Ty3. These types are concurrently expressed and variably combined, evident in both CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). It should be noted that within the context of CRSwNP, type 2 inflammation is the most common variant in the Western population, with an increase in eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. The conventional treatment approach includes the utilization of local and systemic corticosteroids, and/or sinonasal surgery. However, these strategies might be associated with recurring instances, potentially requiring further surgical revisions. “ Difficult-to-treat patients ” often exhibit more severe conditions, requiring elevated systemic corticosteroid doses and/or undergoing multiple sinonasal surgeries. Literature findings indicate that biologic agents, targeting specific key effectors of type 2 inflammation, may serve as an additional therapy for individuals with severe and uncontrolled CRSwNP, resulting in significant improvement across various outcomes. Therefore, the importance of disease endotyping has progressively grown over the years. The correct definition of the target patient, the type of biologic drug to be used and the timing of intervention are crucial to ensure personalized therapy and optimize the cost/effectiveness of the treatment. Randomized controlled trials (RCTs) have shown significant improvements in both objective and subjective parameters. However, the results of these RCTs are not necessarily applicable to daily practice. The aim of this retrospective study is to assess the therapeutic impact of biologics in patients with CRSwNP within a real-world context. Patients treated with one of the AIFA-approved biologics (dupilumab, omalizumab and mepolizumab) since April 2023 with at least 9 months of follow-up VI were included in the study. Changes in Sinonasal Outcome Test 22 (SNOT-22) and Nasal Polyp Score (NPS), as well as subjective changes in sense of smell, changes in serum total IgE levels and total eosinophil counts, comorbidities, discontinuation or change in monoclonal antibody and adverse events were assessed. Thirty-three patients were included in the study. All agents produced significant improvements in polyp size, symptom severity and subjective olfactory assessment. The monoclonal antibody had to be changed in no patients. No serious adverse events occurred during treatment initiation and follow-up. This analysis showed a moderate superiority of dupilumab, particularly in terms of rapid onset of action, in improving signs, symptoms and quality of life in CRSwNP. Biological treatments emerge as a promising option for patients with severe refractory CRSwNP. The efficacy of biologics is evident in randomized controlled trials and real-world clinical settings, demonstrating substantial improvements in the evaluation of nasal polyps and related symptoms. Moreover, the incidence of complications associated with biologics in this context is rare. Advances in statistical methodologies, head-to-head comparative trials, and comprehensive real-life studies are essential to establish more definitive conclusions and elucidate the precise roles of individual biologic agents.